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Pancreatic A and B cell hyperfunction in the Mendenhall syndrome
Abstract:
A 16-year-old boy with persistent hyperglycaemia (approximately 16 mmol/l in the fasting state) and acanthosis nigricans had insulin resistance and received daily up to 2800 U of short-acting, soluble, highly purified porcine insulin. The number and affinity of insulin receptors were markedly decreased. No significant insulin binding to IgG could be detected. Immunoreactive insulin varied between 1344 and 2400 mU/l. Endogenous insulin secretion and proinsulin levels were grossly elevated in the fasting state (C-peptide 2.2-3.5 pmol/ml; proinsulin approximately 1 pmol/ml). After an oral glucose tolerance test and intravenous arginine infusion, B cell hypersecretion was confirmed. The molar ratio of C-peptide to immunoreactive insulin, normally approximately 7, was about 0.3, clearly indicating that most of the immunoreactive insulin was exogenous. The molar ratio of proinsulin to C-peptide, which is about 0.05 in fasting control subjects, was 0.23-0.45, clearly showing that too high a proportion of proinsulin was being secreted. This may indicate that the constant hyperstimulation of the B cell leads to reduced conversion of proinsulin to insulin. Immunoreactive glucagon levels were within normal limits fasting but were above normal after intravenous arginine infusion. Thus, in this case of diabetes with acanthosis nigricans, the severe insulin resistance, probably caused by a receptor defect, was associated with markedly increased B cell function.
Insights
This study examines a teenager with severe insulin resistance and acanthosis nigricans, finding a receptor defect and B cell hypersecretion. High exogenous insulin levels were confirmed, indicating the body
Area of Science:
- Endocrinology
- Metabolic Disorders
- Molecular Biology
Background:
- Investigating severe insulin resistance in adolescents presenting with acanthosis nigricans.
- Understanding the role of insulin receptors and endogenous insulin secretion in complex metabolic conditions.
Observation:
- A 16-year-old male exhibited persistent hyperglycemia (16 mmol/l fasting) and acanthosis nigricans, indicative of significant insulin resistance.
- Markedly decreased insulin receptor number and affinity were observed, alongside extremely high levels of immunoreactive insulin (1344–2400 mU/l).
- Elevated endogenous C-peptide (2.2–3.5 pmol/ml) and proinsulin (approx. 1 pmol/ml) levels suggested B cell hypersecretion.
Findings:
- Analysis revealed a low C-peptide to immunoreactive insulin molar ratio (approx. 0.3), confirming predominantly exogenous insulin administration.
- A high proinsulin to C-peptide molar ratio (0.23–0.45) indicated impaired proinsulin conversion, potentially due to chronic B cell overstimulation.
- Immunoreactive glucagon levels were normal fasting but elevated post-arginine infusion.
Implications:
- The findings suggest a severe insulin receptor defect as the primary cause of insulin resistance in this case.
- Chronic B cell hyperstimulation may lead to functional impairment, characterized by increased proinsulin secretion.
- This case highlights the complex interplay between receptor defects, exogenous insulin use, and endogenous pancreatic beta-cell function in severe insulin resistance syndromes.